This research is concerned with the problem of calculating protein structure. The aim is to determine how interatomic interactions lead to the native three- dimensional structure of a protein. The methods used are based on statistical mechanics, relying heavily on both theory and computer simulations (Monte Carlo and energy minimization). During the past year, we have continued the derivation of a new force field, as an improvement over our current one (ECEPP). As additional innovations in methodology, we parallelized some of our algorithms for use on the KSR1 computer, made a statistical analysis of side-chain conformations in proteins , developed a method to carry out normal mode analyses of large macromolecules , applied an entropy- sampling Monte Carlo method to identify the basic statistical mechanical features of the protein folding problem , analyzed the electrostatic contribution to the helix-coil transition of poly (L-lysine) in water and aqueous methanol solutions , solved the problem of the end-to-end distribution function for a finite polymer chain, developed methods to pack polypeptide chains and small molecules in arrays and in crystals, and developed a united-residue potential. In addition to the development of methodology, we applied our algorithms to two biological problems, viz., the structure of collagen and the conformation of angiotension II and the mechanism of the activation of its receptor. In as-yet-unpublished work, we have focused much of our effort to surmount the multiple- minima problem arising from the complexity of the energy landscape; most of the attention on this problem is being devoted to improving and implementing our diffusion equation method to smooth out the energy landscape to be able to identify the global minimum. In addition, work is being carried out to complete the development of our new force field and to incorporate hydration into it with the aid of ab initio quantum mechanical and crystal-packing calculations.